Diphtheria toxin (DT) binds to a specific cell surface receptor, gets internalized, and causes cytotoxicity through its catalytic domain. The toxicity of DT is used in several therapeutic molecules. Here, we have exploited the receptor-binding ability of DT to increase cellular uptake of curcumin, a hydrophobic molecule with low bioavailability and cellular uptake. We have expressed only the receptor-binding domain of DT (RDT) in E. coli. Purified RDT binds to the receptor with an affinity equivalent to that of full-length DT. It also binds to curcumin forming curcumin-RDT complex and this increases fluorescence intensity and fluorescence lifetime of curcumin. Curcumin-RDT complex binds to the receptor and associates with human glioblastoma cells (U-87 MG) expressing the receptor. Cellular uptake of curcumin is higher for curcumin-RDT complex than curcumin alone. This increase in uptake enhances the anti-proliferative effect of curcumin and induces apoptosis of these cells even at a lower dose.